Combined-step process for pharmaceutical compositions

Abstract

The invention relates to a process for the solid oral pharmaceutical formulation of a pharmaceutically active ingredient such as levetiracetam, comprising a wet granulation of the pharmaceutically active ingredient and simultaneous fluid bed drying such that, as the pharmaceutical blend granulates it is simultaneously dried thus preventing it from becoming a paste. The invention therein thus provides a novel formulation preparation process characterized by a “combined” Granulation and Fluid Bed Drying process step.

1. A process for the preparation of a solid oral pharmaceutical comprising: (a) wet granulating a pharmaceutical blend comprising a pharmaceutically active ingredient; and (b) simultaneously fluid bed drying the blend, wherein the pharmaceutically active ingredient is levetiracetam, wherein the granules produced are homogeneous and free of agglomerates. 
     
     
       2. The process according to  claim 1 , wherein the wet granulating is performed using a wet granulating agent. 
     
     
       3. The process according to  claim 2 , wherein the wet granulating agent is water. 
     
     
       4. The process according to  claim 2 , wherein the wet granulating agent is sprayed for a spray time of up to about 40 minutes at a spray rate of 200-210 g/min. 
     
     
       5. The process according to  claim 2 , wherein the wet granulating agent is sprayed at spraying rate in the range of 1-20 g/min. 
     
     
       6. The process according to  claim 1 , wherein the fluid bed drying employs an air velocity in the range of 500-600 cfm (850-1020 CMH). 
     
     
       7. The process according to  claim 1 , wherein the fluid bed drying employs an air velocity in the range of 40-100 CMH. 
     
     
       8. The process according to  claim 1 , wherein the solid oral pharmaceutical is a tablet or a capsule. 
     
     
       9. The process according to  claim 8 , wherein the solid oral pharmaceutical is a tablet having an LOD of <4%, a Friability of <0.8% in 4 minutes, and a disintegration time of <15 minutes. 
     
     
       10. The process according to  claim 1 , wherein said solid oral pharmaceutical is useful for the treatment of a Central Nervous System disorder, motion sickness, hyperkinesia, hypertonia, convulsive disorders, memory disorders, hypoxic or ischemic type aggressions of the CNS, bipolar disorders, mania, migraine and chronic or neuropathic pain. 
     
     
       11. The process according to  claim 10 , wherein the convulsive disorder is epilepsy. 
     
     
       12. A pharmaceutical composition prepared by a process comprising: (a) wet granulating a pharmaceutical blend comprising a pharmaceutically active ingredient; and (b) simultaneously fluid bed drying the blend, wherein the pharmaceutically active ingredient is levetiracetam, wherein the granules produced are homogeneous and free of agglomerates. 
     
     
       13. The pharmaceutical composition according to  claim 12 , which is a tablet or a capsule. 
     
     
       14. A method of treating a Central Nervous System disorder, motion sickness, hyperkinesia, hypertonia, convulsive disorders, memory disorders, hypoxic or ischemic type aggressions of the CNS, bipolar disorders, mania, migraine and chronic or neuropathic pain in a patient comprising administering to the patient a pharmaceutical composition prepared by a process comprising: (a) wet granulating a pharmaceutical blend comprising a pharmaceutically active ingredient; and (b) simultaneously fluid bed drying the blend, wherein the pharmaceutically active ingredient is levetiracetam, wherein the granules produced are homogeneous and free of agglomerates. 
     
     
       15. The method according to  claim 14 , wherein the convulsive disorder is epilepsy.